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@ARTICLE{AlfonsoGonzalez:276065,
author = {C. Alfonso-Gonzalez and I. Legnini and S. Holec and L.
Arrigoni and H. C. Ozbulut and F. Mateos and D. Koppstein
and A. Rybak-Wolf and U. Bönisch and N. Rajewsky$^*$ and V.
Hilgers},
title = {{S}ites of transcription initiation drive m{RNA} isoform
selection.},
journal = {Cell},
volume = {186},
number = {11},
issn = {0092-8674},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2023-00971},
pages = {2438-2455.e22},
year = {2023},
note = {2023 May 25;186(11):2438-2455.e22},
abstract = {The generation of distinct messenger RNA isoforms through
alternative RNA processing modulates the expression and
function of genes, often in a cell-type-specific manner.
Here, we assess the regulatory relationships between
transcription initiation, alternative splicing, and 3' end
site selection. Applying long-read sequencing to accurately
represent even the longest transcripts from end to end, we
quantify mRNA isoforms in Drosophila tissues, including the
transcriptionally complex nervous system. We find that in
Drosophila heads, as well as in human cerebral organoids, 3'
end site choice is globally influenced by the site of
transcription initiation (TSS). 'Dominant promoters,'
characterized by specific epigenetic signatures including
p300/CBP binding, impose a transcriptional constraint to
define splice and polyadenylation variants. In vivo
deletion or overexpression of dominant promoters as well as
p300/CBP loss disrupted the 3' end expression landscape. Our
study demonstrates the crucial impact of TSS choice on the
regulation of transcript diversity and tissue identity.},
keywords = {5ʹ-3ʹ coupling (Other) / Drosophila (Other) / alternative
polyadenylation (Other) / human brain organoids (Other) /
long-read sequencing (Other) / mRNA isoform (Other) /
nervous system (Other) / p300/CBP (Other) / transcription
(Other) / transcription start site (Other)},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37178687},
doi = {10.1016/j.cell.2023.04.012},
url = {https://inrepo02.dkfz.de/record/276065},
}